This project intends to analyze the effects of antitumor agents on an established human carcinoma cell line in order to provide useful information relevant to the rational design of chemo- and radio-therapeutic clinical trials. Cell killing, defined as the inability to form colonies, will be studied after exposure to various drug concentrattons or radiation doses at different time schedules. Cell-cycle stage sensitivity will be investigated by treating synchronized cells. Effects on cell progression delay will be studied to define synchronizing agents. Cumulative effects of fractionated doses will be defined to estimate cell recovery. Therapeutic gain will be investigated by combination of drugs given simultaneously or sequentially. Methods will be developed to study the response of resting phase population by the use of plateau phase cultures and multicellular spheroids. BIBLIOGRAPHIC REFERENCE: Drewinko, B. and Yang, L.Y.: Restriction of CEA synthesis to the stationary phase of growth of cultured human colon carcinoma cells. Exp. Cell Res., 101: 414-416, 1976.